November

Novel mechanism for memory formation discovered

How is long-term memory formed? What goes wrong in cognitive disorders such as Alzheimer’s disease? Although important scientific advances have been made towards answering these fundamental questions, the exact mechanism behind long-term memory formation is still unclear. Significant research led by Professor Peter Giese from the Institute of Psychiatry (IoP) at King’s College London has shed some new insight into this matter by discovering a novel mechanism for memory formation.

Currently, the most widely considered mechanism of memory formation is the enhancement of transmission at existing connections between neurones, called synaptic strengthening. This consists of a series of molecular events such as the activation of certain neurotransmitter and kinase systems, calcium influx, the induction of gene expression and the translation and regulation of proteins. These events seem to be affected in various mouse models of cognitive disorder. However, it has emerged that memory formation can still take place despite impaired synaptic strengthening, suggesting that there are other mechanisms involved.

Prof Giese says: ‘Memory deficits are associated with many mental disorders but these cannot be cured due to the lack of mechanistic insights. We have discovered a novel neuronal communication for memory which provides a new direction for studying memory deficits in mental disorders, including autism, Alzheimer's disease, schizophrenia, and post-traumatic stress disorder.’

In a study published last week in the Proceedings of the National Academy of Sciences, the researchers set to find out if the formation of brand new connections between neurones, or synaptogenesis, could be one of those other mechanisms. In order to do so, they studied a mouse model with severely impaired synaptic strengthening and found that formation of contextual long-term memory still occured after a certain number of training trials.

Prof Giese explains: ‘Using a mouse model, we found that after extensive training, memory can be formed due to the generation of multi-innervated spines, specific connections where two neurons connect to another neuron. This type of memory requires not only more training but also appears less flexible than healthy memory.’

This is the first time that multi-innervated spines (MIS) generation has been implicated in memory formation.

Prof Giese adds: ‘Based on the underlying molecular processes, it is likely that various memory deficits in disease are caused by abnormal production of multi-innervated spines. We found that in healthy models MIS generation might occur after extensive training to engrave memory. However, in cognitive disorders MIS generation predominates, slowing down the speed of memory formation and making the acquired memories less flexible.’

For full paper: Radwanska et al., (2011), “Mechanism for long-term memory formation when synaptic strengthening is impaired”, Proceedings of the National Academy of Sciencesdoi:10.1073/pnas.1109680108

For more information, please contact Seil Collins, Press Officer, Institute of Psychiatry at King’s College London, email: seil.collins@kcl.ac.uk or tel: 0207 848 5377. This story was written by Dr Rosa Sancho, Post-doctoral research fellow in Neuroscience.